The present invention relates to spectrophometric analysis and is particularly concerned with a method of, and apparatus for, such analysis of a tablet (primarily material of the tablet) by measurements of a beam of electromagnetic radiation (usually near infrared) transmitted through the tablet.
Spectrophotometric analysis is a well known facility for providing quantitative and qualitative measurements or assessments of organic and biological substances and materials, especially pharmaceutical materials. In the pharmaceutical industry it is necessary to analyse tablets randomly selected from a production batch to ensure that the characteristics of the tablets fall within tolerances of a particular specification; this particularly concerns the identity of the constituents, content uniformity, potency, hardness and thickness of the tablets. The identity, content uniformity and potency of tablet material are of especial importance and a well known and popular technique for assessing these characteristics is by spectrophotometric analysis of reflectance measurements which result from a beam of near infrared (NIR) radiation applied to the material of the tablet. Typical near infrared spectrophotometers suitable for providing reference spectra are sold under the Trade Marks COMPSCAN by The Gardner Neotech Division of Pacific Scientific and MODEL 6500 (together with a Rapid Content analyser) by Foss Electric. It is recognised however that analysis of a tablet per se by near infrared (NIR) reflectance measurements has the disadvantage that it is not possible to clearly distinguish between different tablet types or tablets with varying potency (drug content) or hardness. This is because only the surface of the tablet is scanned.
Therefore only a small part of the tablet sample is analysed and this may not be representative of the whole tablet. For example, reflectance measurements from a typical pharmaceutical tablet will result from near surface regions of the tablet (which are likely to correspond with a penetration depth for the NIR beam in the order of 0.5 millimeters) and clearly this will not provide a reliable indication of the overall structure or characteristics of a tablet whose thickness is considerably in excess of 0.5 millimeters. It has not been possible therefore to rely on NIR reflectance measurements of pharmaceutical tablets to assess whether or not a production batch of those tablets is acceptable for marketing. Because of these problems it is conventional practice to analyse the material of a tablet by destructive testing. This may include reducing the tablet to powder and subjecting it to analysis, including that by NIR reflectance measurements. Such analysis has been found to provide a greater order of accuracy and reliability when effected on a material in powder form as compared with that derived from the material when in tablet form.
Because of the necessity to ensure that the characteristics of the material of a pharmaceutical tablet meet a predetermined specification, the procedure for analysing tablets at frequent intervals during or following production of a batch of tablets adds considerably to the production cycle time, that is the time it takes to manufacture a tablet from its basic ingredients to when the tablet is packaged ready for marketing. It is not unusual, and indeed may be typical, for an actual manufacturing cycle time of a pharmaceutical tablet to be in the order of five to seven times longer than a theoretically determined manufacturing cycle time. Bearing in mind that it is not unusual for the theoretical manufacturing cycle time to be from five to twenty five days, it will be appreciated that the differential between the theoretical and actual cycle times adds considerably to the manufacturing costs, principally in the costs of administering and storing the pharmaceutical product. An appreciable part of the administration costs results from delays in analysing the characteristics of a tablet to ensure that it attains a predetermined specification and as a consequence a batch of tablets manufactured and ready for marketing may be held up for several days awaiting acceptable analysis reports before they can actually be released to the market.
In an attempt to overcome the disadvantages of the above described tablet analysis techniques it has been proposed to provide a rapid non-destructive quality assessment of tablets using spectrophotometric analysis of a tablet by transmission measurements resulting from a beam of electromagnetic radiation (usually near infrared) passing through the tablet. By this technique the full thickness of the tablet is analysed giving a spectrum which is representative of the whole tablet and this should make it possible to achieve a quick release of tablets during production with the aim of reducing the actual manufacturing cycle time. An example of a spectrophotometer utilising near infrared transmission through a tablet is an analyser sold under the Trade Mark INTACT by Foss Electric. This tablet analyser has a tablet holder in the form of a plate-like body in which a recess is provided, such recess being intended to accommodate a tablet for analysis. In a bottom face of the recess is located an aperture through which NIR radiation transmitted through the tablet is directed to a detector of the spectrophotometer. The detector is responsive to the transmitted radiation and provides measurements for analysing characteristics of a tablet that is located in the recess. The tablet is a close fit in the recess to overlie the aperture whilst the tip of a fibre optic probe (through which the NIR beam is provided) is moved onto the tablet to direct the NIR beam through it. A typical pharmaceutical tablet will have a relatively dense structure and good reflectance characteristics and research has indicated that only (approximately) 0.5% of the intensity of the NIR beam that is applied to the tablet will be transmitted through the tablet to the detectors. As a consequence a through tablet analyser has to be extremely sensitive to respond to the NIR radiation to which its detectors are subjected for analysis purposes; because of this sensitivity our research has indicated that with known methods and apparatus the repeated analysis of a tablet is inconsistent or not reproducible. As a result the analysis of a particular pharmaceutical tablet could not be relied upon to determine whether or not the characteristics required of that tablet had been met to permit a batch of the tablets to be released to the market or for manufacture of the tablets in that batch to continue. By way of example, FIG. A of the accompanying illustrative drawings shows the spectra acquired of a typical pharmaceutical tablet in the tablet analyser as aforementioned in which the ordinate shows a level of absorbence and the abscissa the wavelength. The several graphs were determined from repeated analysis of the same tablet which was removed from the analyser and replaced to be scanned and subjected to analysis on ten successive occasions. For each of the ten scannings the orientation of the tablet in the recess was maintained constant. This was considered to be important as it is usual for tablets to be embossed or otherwise marked on one side face with a trade name or other identification and on the other side face with a score line (along which the tablet may easily be broken) so that changing the orientation of the tablet to present a different side face to the source of NIR radiation could unreasonably have altered the conditions under which the analysis was effected. It will be seen that the graphs indicate a wide variation in the absorbence levels that were determined for a particular wavelength. Accordingly if it is known that a particular pharmaceutical compound to be acceptable in the tablet has to provide absorbence within a predetermined range for a given wavelength and this range of absorbence is less than that exhibited by the extremes of the graphs derived from the analysis results, it would be inappropriate to rely on the analysis in deciding whether or not the constitution of the tablet is acceptable. There is therefore a need for both a method of, and an apparatus for, spectrophotometric analysis of the characteristics of a tablet from measurements of a beam of electromagnetic radiation transmitted through the tablet whereby the analysis is sufficiently accurate and reproducible so that it can be relied upon for determining the acceptability or otherwise of tablets as manufactured and thereby provide a rapid and non-destructive quality assessment to enable the quick release of tablets during production with the aim of reducing the manufacturing cycle time. It is an object of the present invention to provide a method and apparatus for spectrophotometric analysis which lends itself towards satisfying the aforementioned need.